Imatinib Therapy Research Articles

Multiple intratumoral sources of kit ligand promote gastrointestinal stromal tumor.

Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and is typically driven by a single mutation in the Kit or PDGFRA receptor. While highly effective, tyrosine kinase inhibitors (TKIs) are not curative. The natural ligand for the Kit receptor is Kit ligand (KitL), which exists in both soluble and membrane-bound forms. While KitL is known to stimulate human GIST cell lines in vitro, we used a genetically engineered mouse model of GIST containing a common human KIT mutation to investigate the intratumoral sources of KitL, importance of KitL during GIST oncogenesis, and contribution of soluble KitL to tumor growth in vivo. We discovered that in addition to tumor cells, endothelia and smooth muscle cells produced KitL in KitV558Δ/+ tumors, even after imatinib therapy. Genetic reduction of total KitL in tumor cells of KitV558Δ/+ mice impaired tumor growth in vivo. Similarly, genetic reduction of tumor cell soluble KitL in KitV558Δ/+ mice decreased tumor size. By RNA sequencing, quantitative PCR, and immunohistochemistry, KitL expression was heterogeneous in human GIST specimens. In particular, PDGFRA-mutant tumors had much higher KitL expression than Kit-mutant tumors, suggesting the benefit of Kit activation in the absence of mutant KIT. Serum KitL was higher in GIST patients with tumors resistant to imatinib and in those with tumors expressing more KitL RNA. Overall, KitL supports the growth of GIST at baseline and after imatinib therapy and remains a potential biomarker and therapeutic target.

Cytoreductive surgery offers prognostic benefits in metastatic gastrointestinal stromal tumors with generalized progression following imatinib therapy: a single institute retrospective study

BackgroundGastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Distant metastasis has been detected in approximately 50% of GIST patients at the first diagnosis. The surgical strategy for metastatic GIST with generalized progression (GP) after imatinib therapy remains unclear.MethodsWe recruited 15 patients with imatinib-resistant metastatic GIST. They received cytoreductive surgery (CRS) for tumor rupture, intestinal obstruction and gastrointestinal bleeding. We collected clinical, pathological and prognostic data for analyses.ResultsOS and PFS after R0/1 CRS were 56.88 ± 3.47 and 26.7 ± 4.12 months, respectively, when compared with 26 ± 5.35 and 5 ± 2.78 months after R2 CRS (P = 0.002 and P < 0.001, respectively). The OS of patients from the initiation of imatinib in the R0/1 group was 133.90 ± 15.40 months when compared with 59.80 ± 10.98 months in the R2 CRS group. There were two significant grade III complications after 15 operations (13.3%). No patient underwent reoperation. In addition, no perioperative death occurred.ConclusionsR0/1 CRS is highly probable to provide prognostic benefits for patients with metastatic GIST who experience GP following imatinib treatment. An aggressive surgical strategy for achieving R0/1 CRS can be deemed safe. If applicable, R0/1 CRS should be carefully considered in imatinib-treated patients with GP metastatic GIST.

SARS-CoV-2 Omicron BA.5.2-infection and COVID-19 in persons with chronic myeloid leukaemia.

A SARS-CoV-2 Omicron (BA.5.2) epidemic began in China in December, 2022 following stopping the zero COVID policy. We studied features of the epidemic in 1,121 persons with chronic myeloid leukaemia (CML). 1103 (98%) were in chronic, 10 in accelerated and 8 in acute phases. 834 (74%) became infected almost all of whom met criteria for COVID-19. The most common symptoms were fever (91%), cough (90%) and fatigue (82%). 42 infected persons were asymptomatic. Most people quarantined at home and self-medicated. 22 were hospitalized for COVID-19. At admission 5 had mild, 14, moderate and 3, severe/critical disease according to World Health Organization (WHO) criteria. 5 received respiratory assistance, 3 were admitted to the intensive care unit (ICU) and 1 in accelerated phase died from COVID-19. Co-variates associated with a risk of COVID-19 in SARS-CoV-2-infected subjects include age ≥ 65 years, higher education level and imatinib therapy. In conclusion, most SARS-CoV-2 Omicron BA.5.2 infections in persons with CML resulted in COVID-19 most of which cases are mild with only 1 death.

P-264 The effect of preoperative imatinib therapy in gastrointestinal stromal tumors: A multicenter study

P-264 The effect of preoperative imatinib therapy in gastrointestinal stromal tumors: A multicenter study

Oral targeted delivery of Imatinib by pH responsive copolymer modulates liver fibrosis in the mice model

Liver fibrosis is a significant cause of morbidity and mortality without approved treatment. The therapeutic effects of Imatinib as a tyrosine kinase inhibitor on reversing liver fibrosis have already been shown. However, considering the conventional route of Imatinib administration, the amount of drug to be used is very high, and its side effects are raised. Therefore, we designed an efficient pH-sensitive polymer for the targeted delivery of Imatinib in treating a carbon tetrachloride (CCl4)-induced liver fibrosis. This nanotherapeutic system-based Vitamin A (VA)-modified Imatinib-loaded poly (lactic-co-glycolic acid)/Eudragit S100 (PLGA-ES100) has been successfully fabricated by adapting the solvent evaporation technique. The applying ES100 on the surface of our desired nanoparticles (NPs) protects drug release at the acidic pH of the gastric and guarantees the effective release of Imatinib at a higher pH of the intestine.Besides, VA-functionalized NPs could be an ideal efficient drug delivery system due to the high capacity of hepatic cell lines to absorb VA. For induction of liver fibrosis, CCL4 was intraperitoneally (IP) injected twice a week for six weeks in BALB/c mice. Oral administration of VA-targeted PLGA-ES100 NPs loaded with Rhodamine Red™ by live animal imaging showed a preferential accumulation of the selected NPs in the liver of mice. Besides, administrating targeted Imatinib-loaded NPs significantly decreased serum levels of ALT, and AST, and also reduced the expression of extracellular matrix components, including collagen I, collagen III, and α-SMA, considerably. Interestingly, histopathological evaluation of liver tissues through H&E and Masson's trichrome staining showed that oral administration of targeted Imatinib-loaded NPs reduced hepatic damage by enhancing hepatic structure condition. Also, the Sirius-red staining indicated a reduction in collagen expression during treatment with targeted NP containing Imatinib. The immunohistochemistry result on liver tissue shows a significant decrease in the expression of α-SMA in groups treated with targeted NP. In the meantime, administration of a very scarce dose of Imatinib via targeted NP caused a substantial decline in the expression of fibrosis marker genes (Collagen I, Collagen III, α-SMA).Our results confirmed that novel pH-sensitive VA-targeted PLGA-ES100 NPs could efficiently deliver Imatinib to the liver cells. Loading Imatinib in the PLGA-ES100/VA might overcome many challenges facing conventional Imatinib therapy, including gastrointestinal pH, the low concentration at the target region, and toxicity.

CML with De Novo NPM1 Mutation and Rapid Progression to Myeloid Blast Cri-Sis despite Treatment with Imatinib: A Case Report

In this case we present a 41 year old male with chronic myeloid leukaemia who despite scoring low risk for Sokal progressed rapidly to blast crisis without warning and after having achieved a partial response to Imatinib therapy. We investigated using retrospective Next Generation Sequencing (NGS) and identified a novel NPM1 mutation at diagnosis and blast crisis together. We also found tyrosine kinase domain mutations using NGS not found with Sanger sequencing. We believe this case highlights the effectivity of NGS in identifying novel and existing mutations with higher sensitivity, which could help improve existing practice in prognostication and management of CML disease in patients not responding to treatment adequately.

Comparison of morbidity and results of chronic myeloid leukemia treatment in Novosibirsk and the Novosibirsk region

Introduction. Over the past decade significant progress has been made in the treatment of patients with chronic myeloid leukemia (CML). In the most patients it is possible to reach a major molecular response (MMR) and maximize overall survival (OS). However, in real clinical practice in the regions of Russia, there is a number of unresolved problems that have led to the deterioration in the results of therapy such as, low patient compliance to treatment and the lack of proper control by doctors of polyclinics over the intake of medications and the course of the disease. Aim — to compare the incidence and results of therapy of patients with chronic myeloid leukemia in Novosibirsk and the Novosibirsk region. Materials and methods. The results of therapy of 333 CML patients were studied. The incidence and prevalence of disease, 5-year OS and predicted 10-year OS as well as 5-years and 10-years predicted event-free survival (EFS) have been evaluated. Results of therapy and compliance to treatment of 214 patients with CML who had been treated with imatinib for more than 18 months also were studied. Results. The incidence from 2004 for 2020 was 0.62 per 100,000 population per year, the prevalence of CML in Novosibirsk over the past 15 years has increased from 3.27 to 10.89 cases per 100,000 population, in the Novosibirsk region – from 1.83 to 5.55 cases per 100,000 population. Median OS was not reached. The 5-year OS and 10-year OS in Novosibirsk were 85.7 and 72.5 %, respectively. The 5-year OS and 10-year OS in Novosibirsk region was 80.5 and 72.3 %, respectively. The 5-year EFS and 10-years predicted EFS in Novosibirsk was 55.8 and 40.8 %, respectively. The 5-year EFS and 10-years predicted EFS in Novosibirsk region was 34.9 and 18.7 %, respectively (p = 0.02882). The median EFS in Novosibirsk and Novosibirsk region was 6.8 and 2.7 years, respectively. Among patients treated in Novosibirsk, 134 patients (95.7 %) achieved a complete clinical and hematological response (CHR), 124 patients (88.5 %) — a complete cytogenetic response (CCyR), 95 patients (67.8 %) achieved MMR. Treatment failure was in 45 patients who did not obtain MMR and 16 (35.5 %) of 45 did not achieve even CCyR. The 2nd generation tyrosine kinase inhibitors (TKI 2) were administered to 18 patients who were resistant to imatinib. CHR was maintained in 17 out of 18 patients (94.4 %), CCyR — in 14 patients (77.7 %), MMR was achieved in 12 patients (66.7 %). In Novosibirsk region CHR was obtained in 72 of 74 patients (97.3 %), CCyR — in 50 patients (67.6 %), MMR — in 13 patients (17.6 %). No MMR was achieved in 61 patients (82.4 %), 17 (22.9 %) of them failed to obtain even CCyR. TKI 2 were administered to 7 out of these 61 patients, and 6 (85.7 %) of 7 maintained CHR, 5 patients (71.4 %) — CCyR, 1 patient (14.3 %) – MMR. Adherence to imatinib therapy was significantly lower in the group of patients with therapy failure than in patients with an optimal response both in Novosibirsk (p &lt; 0.00001) and in Novosibirsk region (р = 0,000002). Conclusion. We have revealed a significant increase in the incidence of CML in Novosibirsk and Novosibirsk region. The problems in treatment are as follows: insufficient control by primary care physicians over patients living in Novosibirsk region and low treatment compliance of patients.

Long-term outcomes of frontline imatinib therapy for chronic myeloid leukemia in China.

Imatinib is the first-line therapy recommended for chronic myeloid leukemia (CML) patients in China. We reported a long-term follow-up study of patients on imatinib as first-line treatment for chronic phase (CP) CML to provide an important reference for the actual clinical treatment regimen of CML patients in China. We evaluated the long-term efficacy, safety, low-dose attempt after years of treatment, and treatment-free remission (TFR) of 237 CML-CP patients receiving first-line imatinib therapy. The median age was 46 years (interquartile range: 33-55). After a median follow-up of 6.5 years, the cumulative complete cytogenetic response, major molecular response (MMR), and MR4.5 rates were 82.6%, 80.4%, and 69.3%, respectively. The 10-year transformation-free, event-free, and failure-free survival rates were 97.3%, 87.2% and 53.5%, respectively. Fifty-two (21.9%) patients with sustained deep molecular response (DMR) were treated with low-dose imatinib after years of imatinib treatment. No significant differences in the 1-year and 2-year molecular relapse-free survival in MMR and MR4 were observed between the standard-dose and low-dose groups. Twenty-eight (11.8%) patients discontinued imatinib, and the median time to maintain DMR before discontinuation was 8.43 years. Thirteen patients (5.5%) remained in TFR for a median of 43.33 months. No patients transformed to accelerate or blast phase or died. No new, late toxicity was observed, and the most frequent grade 3/4 adverse events were neutropenia (9.3%), anemia (7.6%), thrombocytopenia (6.3%), and rash (4.2%). This study confirmed the long-term efficacy and safety of imatinib for treating Chinese CML patients. Additionally, it demonstrated the feasibility of imatinib dose reduction and TFR attempts in patients with sustained stable DMR after years of imatinib treatment in real-life settings.

A Case Report of Successful Kidney Transplantation in a Patient With Chronic Myelogenous Leukemia (CML) Who Has Been in Remission for 15 Years on Imatinib

For chronic myeloid leukemia (CML), a Philadelphia chromosome-positive myeloproliferative neoplasm, the introduction of tyrosine kinase inhibitors has transformed CML from a lethal disease into a manageable chronic disease with a close-to-normal life expectancy. Active malignancy is an absolute contraindication to kidney transplantation. However, it is controversial whether kidney transplantation can be safely performed in patients with a history of CML who are in remission. We describe the clinical course of a 64-year-old male patient with chronic kidney disease from diabetic nephropathy (DMN) who underwent living donor kidney transplantation. The patient was diagnosed with CML 15 years ago and promptly achieved cytogenetic and molecular biological remission after starting imatinib. After that, he continued imatinib treatment for 15 years and was in remission, but his chronic kidney disease from DMN gradually worsened. A preemptive living donor kidney transplant was performed in July 2020. Imatinib for CML was discontinued because the patient maintained deep molecular remission (DMR) of major molecular response for more than 15 years before kidney transplantation. After kidney transplantation, the transplanted kidney function remained good at approximate serum creatinine levels of 1.1 mg/dL without histopathologic rejection, and the 3 monthly BCR-ABL1 measurement results were negative and are in progress. Thus, he continues to maintain treatment-free remission status without imatinib for 26 months after renal transplantation. In conclusion, this result suggests that CML with long-lasting DMR on imatinib therapy can be considered an inactive malignancy and therefore a relative indication for kidney transplantation.

Tyrosine Kinase Inhibitors Diminish Renal Neoplasms in a Tuberous Sclerosis Model Via Induction of Apoptosis.

Tuberous sclerosis complex (TSC) tumors are presently incurable despite a cytostatic response to mTOR pathway inhibition because recurrence of disease occurs after treatment is discontinued. Here, we explored the hypothesis that inhibiting tyrosine kinase activity in mesenchymal lineage-specific platelet-derived growth factor receptor β (PDGFRβ) signaling in TSC tumors is cytocidal and attenuates tumorigenesis at significantly higher levels than treatment with an mTOR inhibitor. Rapamycin-induced versus tyrosine kinase inhibitor (TKI)-induced renal angiomyolipoma (AML) and pulmonary lymphangioleiomyomatosis (LAM) tumor cells were comparatively analyzed using cell survival assays, RNA sequencing, and bioinformatics to distinguish tumoricidal mechanisms adopted by each drug type. The efficacy of imatinib therapy was validated against spontaneously developing renal cystadenomas in tuberous sclerosis Tsc2+/- mouse models (C57BL/6J mice; N = 6; 400 mg/kg/d; oral gavage) compared with Tsc2+/- mice treated with PBS (C57BL/6J mice; N = 6). Our study revealed that TKIs imatinib and nilotinib were cytocidal to both pulmonary LAM and renal AML cell cultures through the downregulation of the glycoprotein GPVI pathway and resultant disruption in mitochondrial permeability, increased cytosolic cytochrome C, and caspase 3 activation. Importantly, renal tumor growth was significantly attenuated in imatinib-treated Tsc2+/- mice compared with PBS treatment. The preclinical studies reported here provide evidence documenting the effectiveness of TKIs in limiting LAM and AML cell growth and viability with important clinical potential. Furthermore, these drugs elicit their effects by targeting a PDGF pathway-dependent apoptotic mechanism supporting the investigation of these drugs as a novel class of TSC therapeutics.

CNS-Isolated Blast Crisis in A Patient with Chronic Myeloid Leukemia on Dasatinib (P10-13.004)

<h3>Objective:</h3> NA <h3>Background:</h3> Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by increased cellular proliferation of myeloid precursors and mature cells due to formation of the BCR-ABL proto-oncogene. Blast crisis is characterized as a rapid expansion of a population of myeloid or lymphoid blast cells and defined as &gt;20% blasts in bone marrow or blood. Extramedullary blast crises isolated to the central nervous system are extremely rare, limited to few case reports. <h3>Design/Methods:</h3> NA <h3>Results:</h3> We present a 57 year old male with history of CML since October 2020 on dasatinib 70mg daily who presented with complaints of daily occipital headaches for three months. Exam notable for persistent encephalopathy and unsteady gait. Peripheral serology was unrevealing, suggesting complete hematologic response to dasatinib. MRI brain revealed diffuse leptomeningeal enhancement, as well as small regions of parenchymal enhancement in left frontal lobe, right optic nerve, and lower lying tonsils to suggest early tonsillar herniation. Patient subsequently received left frontal open biopsy and CSF drainage. CSF analysis was unremarkable except for atypical cells. Biopsy of the leptomeninges revealed focal areas consistent with aggregation of myeloid blast cells. Peripheral blood RT-PCR showed BCR-ABL positivity in BCR-ABL1 subtype e13a2 (b2a2, p210) at 0.0788%, which is still consistent with major cytogenetic response to dasatinib. Patient was transferred to outside hospital for evaluation of hematopoietic stem cell transplant. <h3>Conclusions:</h3> Isolated CNS blast crises are rare, with a few cases in the hematological literature, reporting occurrence in patients on chronic imatinib or dasatinib therapy. This may be due to poor CNS penetration of these medications. Here, we demonstrate a patient that had complete hematologic response and major cytogenetic response to dasatinib systemically but with extensive CNS involvement. It is therefore important to have appropriate workup for neurological symptoms with patients with CML despite appearing in chronic phase of the hematological illness. <b>Disclosure:</b> Dr. Puccio has nothing to disclose. Dr. Rodriguez Lee has nothing to disclose. Dr. Song has nothing to disclose.

Spontaneous Non-Traumatic Mediastinal Hematoma in a Patient on Imatinib Therapy for a Gastrointestinal Stromal Tumor (GIST)

Mediastinal hematomas are thoracic complications often resulting from direct trauma or aortic dissections. Spontaneous non-traumatic mediastinal hematomas are rare. We present a case of spontaneous non-traumatic mediastinal hematoma in a patient on Imatinib therapy for a gastrointestinal stromal tumor (GIST). A 67-year-old female presented to the ER with the chief complaint of constant sharp right shoulder pain that progressed to her chest. The patient was not on any anticoagulants and had not complained of shortness of breath. Under suspicion of a pulmonary embolism, a CT chest scan was performed, and a diagnosis of non-traumatic anterior mediastinal hematoma was confirmed. This case may warrant further investigation into the links between Imatinib use and the formation of mediastinal hematomas.

Role of miRNA -150 between different BCR-ABL p210 transcript levels and between different levels of imatinib optimal response in CML patients

The dysregulation of miRNA expression patterns is one of the many effects developments of cancer, miRNA has been found to express abnormally in hematological neoplasia such as chronic myeloid leukemia and solid malignancies. Resistance and the degree of response following tyrosine kinase inhibitor treatment are correlated with miRNA expression. Hence, in this study we tried to study the relationship of miRNA-150 between different breakpoint cluster region–Abelson (BCR- ABL) P210 transcript levels and the role miRNA- 150 between different levels of imatinib optimal response in chronic myeloid leukemia (CML). Our study included sixty chronic myeloid leukemia (CML) patients they were divided into two groups based on response to imatinib therapy, thirty samples of the optimal molecular response of chronic myeloid leukemia (CML) patients, and thirty samples of failure molecular response chronic myeloid leukemia (CML) patients. Thirty samples of apparently healthy volunteers were included and evaluated as control. According to the P210 BCR-ABL%, the results showed a significant difference (P= &lt; 0.0001) between the responder and the failure response CML patients. Assessed the result of miRNA-150 showed a significant difference between both CML patients (P = &lt; 0.0001), assessed miRNA-150 level among different response groups, and failure response of CML patients (P = 0.0002). A cutoff value of response vs. failure response (1.784) with high sensitivity can be a diagnostic value to differentiate between response and failure response. Changing gene expression with different amounts of miRNAs had an impact on drug-gene interactions, with consequences for cell growth and death. Gene expression of different levels miRNA-150 among of CML patients of imatinib therapy showed high expression in response patients than failure response patients. The gene expression level of miRNA-150 differs through different responses in CML patients.

Anlotinib dramatically improved pulmonary hypertension and hypoxia caused by Pulmonary Tumor Thrombotic Microangiopathy (PTTM) associated with gastric carcinoma: a case report

BackgroundPulmonary tumor thrombotic microangiopathy (PTTM) is a rare malignancy-related respiratory complication, demonstrating rapid progression of pulmonary hypertension (PH) and respiratory failure. Although a number of treatments have been attempted for patients diagnosed with or suspected of having PTTM, successful-treated cases of PTTM were mainly from imatinib therapy, which was a PDGF receptor inhibitor. Anlotinib was a novel tyrosine kinase inhibitor that targets VEGFR, FGFR, PDGFR, and c-kit.Case presentationWe reported a patient of PTTM associated with gastric carcinoma, whom were treated with anlotinib, thereby exhibiting significant improvement of PH and respiratory dysfunction.ConclusionOur case provides a new understanding of therapy to PTTM, with implications for defining anlotinib as candidate drug for PTTM. Clinical diagnosis and prompt initiation of anlotinib might be one of the strategies in patients with unstable PTTM.

Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal Tumors.

Gastrointestinal stromal tumors (GISTs) are the most common malignant mesenchymal neoplasms of the gastrointestinal tract. The gold standard for the diagnosis of GISTs is morphologic analysis with an immunohistochemical evaluation plus genomic profiling to assess the mutational status of lesions. The majority of GISTs are driven by gain-of-function mutations in the proto-oncogene c-KIT encoding the tyrosine kinase receptor (TKR) known as KIT and in the platelet-derived growth factor-alpha receptor (PDGFRA) genes. Approved therapeutics are orally available as tyrosine kinase inhibitors (TKIs) targeting KIT and/or PDGFRA oncogenic activation. Among these, imatinib has changed the management of patients with unresectable or metastatic GISTs, improving their survival time and delaying disease progression. Nevertheless, the majority of patients with GISTs experience disease progression after 2-3 years of imatinib therapy due to the development of secondary KIT mutations. Today, based on the identification of new driving oncogenic mutations, targeted therapy and precision medicine are regarded as the new frontiers for GISTs. This article reviews the most important mutations in GISTs and highlights their importance in the current understanding and treatment options of GISTs, with an emphasis on the most recent clinical trials.

The role of miRNA- 96 and miRNA-150 between different BCR-ABL p210 transcript levels and between different levels of imatinib optimal response in CML patients

BackgroundDysregulation of miRNA expression patterns is one of the several effects developments of cancer. MiRNA has been found to express abnormally in hematological neoplasia such as chronic myeloid leukemia and solid malignancies. Resistance and the degree of response following tyrosine kinase inhibitor (TKI (treatment are correlated with miRNA expression. Hence this study has evaluated the correlation between miRNA- 96 and miRNA-150 with different p210 BCR-ABL transcript levels and the role of miRNA- 96 and miRNA-150 at different levels of imatinib optimal response in CML patients. MethodThis study is based on 60 CML patients divided into two groups based on response to imatinib therapy. 30 samples have the optimal molecular response of CML patients. The other 30 samples that have failed molecular response CML patients, which were compared to 30 samples of healthy volunteers as control by depending on the results of CBC film and PCR. BCR-ABL 210 transcript, which was used in this study, is obtained from the patient's file. ResultsThe results based on the comparison of transcript levels showed that there was a significant difference between the positive response and failed response of CML patients (P ≤ 0.0001). The result of miRNA-96 showed that there was no noteworthy difference within both CML patients (P ≥ 0.5030), while miRNA-150 results exhibited a high significant difference (P ≤ 0.0001). The miRNA-96 and miRNA-150 expression levels in all responses of CML patients demonstrated a highly significant difference with P = 0.0134 and P = 0.0002, respectively. The cut-off value of response against failure response of miRNA-96 and miRNA-150 with P value of 1.691 and 1.784, respectively with high sensitivity is a diagnostic value of the difference between the response and failure response. Conclusionmodulating gene expression with different of miRNAs expression has an impact on drug-gene interactions, with consequences for cell growth and death. The gene expression that shows the different level miRNAs (miRNA- 96 and miRNA-150) among of CML patients of imatinib therapy exhibited high expression in response patients than that of the failure response of patients. The gene expression level of miRNA- 96 and miRNA-150 was differed between through different response CML patients.

Longitudinal Gastrectomy Associated with Splenectomy, Caudal Pancreatectomy and Left Hepatectomy for Locally Advanced GIST after Neoadjuvant IMATINIB Therapy: Case Report

Gastro intestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastro intestinal tract [1] and account for 80 % of all GI tumors. Approximately 30% of GISTs are malignant [2]. Occurring throughout the entirety of the GI tract, GISTs most commonly present in the stomach or small intestine [3], Most GISTs present asymptomatically. They are best identified by computed tomography (CT) scan and most stain positive for CD117 (C- Kit). For localized, resectable tumors, surgical resection remains the cornerstone of treatment. For patients with locally advanced disease, preoperative imatinib can be used to help reduce tumor burden before resection [4]. We report the case of a 48 years old patient who presented a gastric stromal tumor invading the spleen, the pancreas and a portion of the left liver. After 6 months of néo adjuvant Imatinib therapy, the patient has undergone a longitudinal gastrectomy associated with splenectomy caudal pancreatectomy and left hepatectomy in which the evolution was favorable.

To Study Demographic Profile, Risk Stratification, and Response to Treatment in Chronic Myeloid Leukemia Patients

Abstract Background: Chronic myeloid leukemia (CML) is the most common leukemia in India. The annual incidence of CML in India was originally reported to be 0.82.2 per 100,000 population. CML is a clonal disorder that is usually easily diagnosed by the Philadelphia chromosome. The approval of tyrosine kinase inhibitors has significantly reduced the mortality rate associated with CML and revolutionized treatment. Materials and Methods: Eighty patients diagnosed with CML were studied. Investigations were done and with European Treatment and Outcome Study (EUTOS) patients were stratified into low- and high-risk group and then treatment with Imatinib was given to all patients and molecular response was evaluated. Results: In the study population, out of 80 patients, 40 were female and 40 were male with M: F is 1:1. Out of total 80 patients’, maximum patients (54) were in 31-60 years age group. Our study showed that the most common symptom of presentation is abdominal discomfort followed by fever. Out of total 80 patients, 25 (31.3%) patients had high EUTOS score and 55 (68.8%) patients had low EUTOS score. On 6 months’ follow-up, 36.3% patients had complete molecular response, 16.3% patients had major molecular response and 47.5% patients had no molecular response, but on 12 months’ follow-up, 71.3% patients had complete molecular response, 16.25% patients had major molecular response, and 12.5% patients had no molecular response. Conclusion: In this observational study, we found a significant correlation between EUTOS score and molecular response at 6 months and 12 months follow-up after Imatinib therapy. Chronic myeloid leukemia, European treatment and outcome study score, response, tyrosine kinase inhibitor

A scoring system to predict molecular responses in patients with chronic myeloid leukemia in the chronic phase receiving initial imatinib therapy

Objective: To develop a scoring system to predict molecular responses in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving initial imatinib therapy. Methods: Data from consecutive adults with newly diagnosed CML-CP treated by initial imatinib was interrogated and subjects were distributed randomly into training and validation cohort, in a ratio of 2∶1. Fine-gray models were applied in the training cohort to identify co-variates of predictive value for major molecular response (MMR) and MR4. A predictive system was built using significant co-variates. The predictive system was then tested in the validation cohort and the area under the receiver-operator characteristic curve (AUROC) was used to estimate accuracy of the predictive system. Results: 1 364 CML-CP subjects receiving initial imatinib were included in this study. Subjects were distributed randomly into training cohort (n=909) and validation cohort (n=455) . In the training cohort, the male gender, European Treatment and Outcome Study for CML (EUTOS) Long-Term Survival (ELTS) intermediate-risk, ELTS high-risk, high WBC (≥130×10(9)/L or 120×10(9)/L, MMR or MR4) and low HGB (<110 g/L) at diagnosis were significantly related with poor molecular responses and were given points based on their regression coefficients. For MMR, male gender, ELTS intermediate-risk and low HGB (<110 g/L) were given 1 point; ELTS high-risk and high WBC (≥130×10(9)/L) , 2 points. For MR4, male gender was given 1 point; ELTS intermediate-risk and low HGB (<110 g/L) were given 2 points; high WBC (≥120×10(9)/L) , 3 points; ELTS high-risk, 4 points. We divided all subjects into 3 risk subgroups according to the predictive system above. Cumulative incidence of achieving MMR and MR4 in 3 risk subgroups was significantly different in both training and validation cohort (all P values <0.001) . In the training and validation cohorts, the time-dependent AUROC ranges of MMR and MR4 predictive systems were 0.70-0.84 and 0.64-0.81, respectively. Conclusions: A scoring system combining gender, WBC, HGB level and ELTS risk was built to predict MMR and MR4 in CML-CP patients receiving initial imatinib therapy. This system had good discrimination and accuracy, which could help phsicians optimize the selsction of initial TKI-therapy.

Prostate cancer, chronic myelogenous leukemia and multiple myeloma in a single patient: a case report and review of the literature

BackgroundSynchronous or metachronous multiple primary malignancies (MPMs) are a known phenomenon. These occurrences may be spontaneous or related to environmental risk factors or genetic predisposition. Chronic myelogenous leukemia (CML) and Multiple myeloma (MM) are two uncommon hematologic malignancies, arises from two different cell lineage. The coexistence of CML and MM that is a rare phenomenon, with only 29 cases reported in the literature. To the best of our, this combination of triple primary cancers has not been reported in a single patient.Case presentationHerein, we reported a case of an 85-year-old Iranian male with three confirmed primary malignant neoplasms. The patient presented with synchronous prostate cancer and CML, in august 2016. He received imatinib and nilotinib for CML and hormonal therapy for prostate cancer. He remained in good control at further follow-ups for about 5 years. In the follow-up period and after 61 months treatment with tyrosine kinase inhibitors (TKIs), CML was undetectable in molecular tests, but the presence of serum M-protein, abnormal plasma cells in the bone marrow, and CRAB criteria was compatible with MM.ConclusionWe must evaluate the possibility of multiple primary cancers during cancer treatment and follow-up and it may be worthwhile to monitor serum electrophoresis and protein levels in TKIs-treated patients.